Efficacy of Perindopril to Prevent Recurrence of Atrial Fibrillation in Patients With Essential Hypertension

NCT ID: NCT00461903

Last Updated: 2020-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 316 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2015-09-30

Brief Summary

The purpose of this 7- to 13-month study is to determine the efficacy of 8 mg/day oral perindopril to prevent the recurrence of atrial fibrillation (AF) in patients with essential hypertension.

Detailed Description

Hypertension affects approximately 50 million individuals in the United States and approximately 1 billion individuals worldwide. As the population ages, the prevalence of hypertension is expected to increase even further unless broad and effective preventive measures are implemented. Recent data from the Framingham Heart Study suggest that individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension. The relationship between blood pressure (BP) and risk of cardiovascular disease (CVD) events is continuous, consistent, and independent of other risk factors. The higher the BP, the greater is the chance of myocardial infarction, heart failure (HF), stroke, and kidney disease.

Atrial fibrillation (AF) is also a major health problem and has been described as one of two emerging cardiovascular epidemics at the turn of the century. It is the most frequent cardiac arrhythmia, affecting 5% of individuals aged > 65 years, and it is associated with an increased risk of stroke and a doubling of all-cause mortality. The loss of effective atrial contraction may result in impaired cardiac performance, reduced exercise tolerance and congestive heart failure. In addition, patients with atrial fibrillation often have disabling palpitations.

Perindopril (Coversyl) is an angiotensin-converting enzyme (ACE) inhibitor with demonstrated efficacy in controlling hypertension. There are several lines of evidence suggesting that ACE inhibition may reduce the incidence of new-onset AF as well as AF recurrences.

Conditions

Essential Hypertension; Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo (for perindopril)

Sugar pill manufactued to mimic perindopril

Group Type: PLACEBO_COMPARATOR

Perindopril

Intervention Type: DRUG

Perindopril 4 mg or matching placebo , 1 tablet administrated once daily for the first 2 weeks. If tolarable, dosage increased to 8mg/day until the end of the study (

Perindopril

Perindopril (coversyl) 4 mg tablets

Group Type: ACTIVE_COMPARATOR

Perindopril

Intervention Type: DRUG

Perindopril 4 mg or matching placebo , 1 tablet administrated once daily for the first 2 weeks. If tolarable, dosage increased to 8mg/day until the end of the study (

Interventions

Perindopril

Perindopril 4 mg or matching placebo , 1 tablet administrated once daily for the first 2 weeks. If tolarable, dosage increased to 8mg/day until the end of the study (

Intervention Type: DRUG

Other Intervention Names

Coversyl

Eligibility Criteria

Inclusion Criteria

• Patients must be age 18 years or older.
• Patients may be either male or female without childbearing potential (or with adequate contraception).
• Patients must have a current diagnosis of essential hypertension with systolic blood pressure (SBP) ≤ 160 mmHg and diastolic blood pressure (DBP) ≤ 100 mmHg at the time of inclusion visit AND
• Patients must have had at least one episode of symptomatic paroxysmal or persistent atrial fibrillation within the preceding six months:

• With an indication for cardioversion in the case of persistent AF
• With electrocardiogram (ECG) documentation of AF
• With duration of an AF episode of at least 10 minutes

Exclusion Criteria

• Unlikely to co-operate in the study
• Pregnancy, breastfeeding, or possibility of becoming pregnant during the study (patients must have adequate contraception as determined by the investigator).
• Alcoholism or drug abuse
• Participation in another study at the same time or within 30 days of randomisation.
• Left ventricular systolic dysfunction with an ejection fraction of 45% or less
• Myocardial infarction within the past month prior to the selection visit
• Cardiac or thoracic surgery within the past 3 months or likely to be performed during the trial
• Chronic AF (continuously present for > 6 months)
• AF secondary to an acute reversible condition (e.g. post-operative atrial fibrillation, hyperthyroidism)
• Currently requiring class I or class III anti-arrhythmic drug therapy (for atrial fibrillation or any other arrhythmia)
• Any medical condition that makes the patient an unsuitable candidate in the investigator's opinion
• Any medical condition requiring ACE inhibitor or angiotensin-receptor blocker therapy (e.g. diabetes, known proteinuria of more than 300 mg per day)
• Renal insufficiency with serum creatinine of 180 μmol/L or greater
• Known bilateral renal artery stenosis
• Serum potassium of 5.0 mmol/L or greater on recent laboratory exam
• Positive pregnancy test (beta human chorionic gonadotropin [HCG] performed in women of childbearing potential)
• Known intolerance to ACE inhibitor
• Impossibility to discontinue certain treatments at selection visit
• Known contraindication(s) to perindopril
• Severe known liver disease including cirrhosis, biliary obstruction or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation more than 3 times the upper limit of normal
• Use of ACE inhibitor or angiotensin-receptor blocker in the 3 months before the inclusion visit
• Severely uncontrolled hypertension with SBP > 160 mmHg or DBP > 100 mmHg at the inclusion visit.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Servier

INDUSTRY

Sponsor Role: collaborator

Montreal Heart Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mario Talajic, MD

Role: PRINCIPAL_INVESTIGATOR

Montreal Heart Institute

Locations

Montreal Heart Institute

Montreal, Quebec, Canada

Countries

Canada

References

Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002 Dec 14;360(9349):1903-13. doi: 10.1016/s0140-6736(02)11911-8.

Reference Type: RESULT

PMID: 12493255 (View on PubMed)

Other Identifiers

IC4-9490-123-CAN

Identifier Type: -

Identifier Source: org_study_id